Cornea is a connective tissue matrix formed from collagen, proteoglycans, other proteins, salts and water. These constituents are similar to those found in other connective tissues such as sclera, but differences in composition and structural organisation permit the cornea to fulfill a unique dual role, combining strength with a high level of transparency. Knowledge of the structural relationship between these various components is essential in understanding their function in health and the breakdowns which occur in disease. This research proposal will provide insight into this relationship. The objective is to determine the structural organisation of collagen, proteoglycans and glycoproteins in the normal human cornea and to study the changes which occur in certain pathological conditions, in particular macular corneal dystrophy, a disease known to involve proteoglycan changes. To evaluate the extent to which individual constituents may vary without affecting transparency, human corneas will be compared to corneas from a range of other animals as well as with sclera. The emphasis is on tissue as nearly as possible in the living state. Synchrotron X-ray techniques and electron microscopy will be used to study the electron density pattern along the collagen fibrils and the arrangement of fibrils within the corneal stroma. In collaboration with Professor J.E. Scott (Manchester University) we will use newly-developed dyes to locate proteoglycans specifically. We have also prepared corneas in which some characterised glycosaminoglycans and glycoproteins have been extracted by biochemical means. By combining electron-microscopical, biochemical immunological and high energy X-ray techniques, we shall identify and locate organic molecules in the corneal architecture.